1 The evidence-based use of prescription medications has led to substantial improvement in healthy aging. 2 Despite this, the use of medications by patients and providers remains suboptimal. Many patients are not 3 prescribed guideline-recommended therapies from which they would benefit; among those for whom 4 appropriate treatment is initiated, almost half do not adhere over the long-term; and, others receive potentially- 5 hazardous medications with an unfavorable balance of risks and benefits. The result: preventable adverse 6 health outcomes and health spending for middle-aged and older adults. 7 While many factors influence the suboptimal use of prescription medications, individual, interpersonal and 8 institutional behaviors are central. As a result, existing intervention to address these issues have attempted to 9 remind, reward, motivate, simplify or otherwise change behavior. Unfortunately, these interventions have only 10 been modestly effective and even among those that are effective, behavior change is rarely sustained over the 11 long-term. The results can be explained by the lack of integrating behavioral principles when designing 12 interventions, a limited focus on evaluating how to deliver them over the long term, and the inherent challenges 13 in delivering precise and personalized behavior change at population scale. 14 Thus, the Brigham and Women's Hospital Roybal Center for Therapeutic Optimization using Behavioral 15 Science will focus on the thematic area of sustaining behavior change, with the following specific aims: (1) to 16 create a translational research program for the development of principle-driven, potent, practical, scalable and 17 sustainable behavioral interventions to enhance the appropriate prescribing and use of evidence-based 18 medications; (2) to strategically direct and to provide scientific oversight, project management, fiscal and 19 operational support to ensure the successful completion of pilot projects funded by the Center through the 20 Administrative Core; and (3) to conduct rigorous pilot studies evaluating principle-driven interventions that aim 21 to sustain behavior change for the use of evidence-based medications through the Pilot Core. 22 The proposed pilots for Year 1 will be Stage I studies, with Stage 0 components, evaluating principle- 23 driven interventions, optimizing message framing through reinforcement learning and repetition-cue-rewards, 24 to improve medication non-adherence. Pilots in subsequent years will specifically solicit applications that 25 address other behaviors (i.e. under and over-prescribing), a broader range of health conditions that impact 26 healthy aging, including cognitive impairment, and that can be conducted in other practice settings and delivery 27 systems, including with health insurers and large employers. 28 The expected impact of the Roybal Center for Therapeutic Optimization using Behavioral Science is that it 29 will develop principle-driven interventions that will readily translate to improvements in healthy aging and will 30 also advance our fundamental understanding of how health behaviors can be effectively sustained.